DOI: 10.1111/epi.17843 ISSN: 0013-9580

A real‐world comparison among third‐generation antiseizure medications: results from the COMPARE study

Roberta Roberti, Gianfranco Di Gennaro, Francesca Anzellotti, Dario Arnaldi, Vincenzo Belcastro, Simone Beretta, Giovanni Boero, Paolo Bonanni, Laura Canafoglia, Alfredo D’Aniello, Filippo Dainese, Carmen De Caro, Giancarlo Di Gennaro, Roberta Di Giacomo, Jacopo C. DiFrancesco, Fedele Dono, Giovanni Falcicchio, Edoardo Ferlazzo, Nicoletta Foschi, Silvia Franciotta, Antonio Gambardella, Alfonso Giordano, Luigi Francesco Iannone, Angelo Labate, Angela La Neve, Simona Lattanzi, Ugo Leggio, Claudio Liguori, Marta Maschio, Annacarmen Nilo, Francesca Felicia Operto, Angelo Pascarella, Giada Pauletto, Rosaria Renna, Gionata Strigaro, Emilio Russo,
  • Neurology (clinical)
  • Neurology



There is little comparative data on the third‐generation antiseizure medications (ASMs). We aimed to assess and compare the effectiveness of brivaracetam (BRV), eslicarbazepine acetate (ESL), lacosamide (LCM) and perampanel (PER) in people with epilepsy (PWE). Efficacy and tolerability were compared as secondary objectives.


A multicenter, retrospective study collecting data from 22 Italian neurology/epilepsy centres. All adult PWE who started add‐on treatment with one of the studied ASMs between January 2018 and October 2021 were included. Retention rate was established as effectiveness measure and described using Kaplan‐Meier curves and the best fitting survival model. The responder status and the occurrence of adverse events (AEs) were used to evaluate efficacy and safety, respectively. The odds of AEs and drug‐efficacy were estimated by two multilevel logistic models.


960 patients (52.92% females, median age 43 years) met the inclusion criteria. They mainly suffered from structural epilepsy (52.29%) with monthly (46.2%) focal seizures (69.58%). Compared with LCM, all the studied ASMs had a higher drop‐out risk, statistically significant in the BRV levetiracetam (LEV)‐naïve (HR: 1.97; 95% CI: 1.17‐3.29) and PER groups (HR: 1.64; 95% CI: 1.06‐2.55). Women were at higher risk of discontinuing ESL (HR: 5.33; 95% CI: 1.71‐16.61), as well as PER‐treated patients with unknown epilepsy aetiology vs those with structural aetiology (HR: 1.74; 95% CI: 1.05‐2.88). BRV with prior LEV therapy showed lower odds of efficacy (OR: 0.08; 95% CI: 0.01‐0.48) vs LCM, whilst a higher efficacy was observed in women treated with BRV and LEV‐naïve (OR: 10.32; 95% CI: 1.55‐68.78) vs men. PER (OR: 6.93; 95% CI: 3.32‐14.44) and BRV in LEV‐naïve patients (OR: 6.80; 95% CI: 2.64‐17.52) had a higher chance of AEs than LCM.


Comparative evidence from real‐world studies may help clinicians to tailor treatments according to patients’ demographic and clinical characteristics.

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